Telethon Kids Institute, The University of Western Australia, Perth, Australia.
School of Paediatrics and Child Health, The University of Western Australia, Perth, Australia.
Immun Inflamm Dis. 2018 Mar;6(1):143-153. doi: 10.1002/iid3.206. Epub 2017 Nov 10.
Infections by rhinovirus (RV) species A and C are the most common causes of exacerbations of asthma and a major cause of exacerbations of other acute and chronic respiratory diseases. Infections by both species are prevalent in pre-school and school-aged children and, particularly for RV-C, can cause severe symptoms and a need for hospitalization. While associations between RV infection and asthma are well established, the adaptive immune-mechanisms by which RV infections influence asthma exacerbations are yet to be defined.
The aim of this study was to characterize and compare T-cell responses between RV-A and RV-C and to test the hypothesis that T-cell responses would differ between asthmatic children and healthy controls.
A multi-parameter flow cytometry assay was used to characterize the in vitro recall T-cell response against RV-A and RV-C in PBMCs from children with acute asthma (n = 22) and controls (n = 26). The responses were induced by pools of peptides containing species-specific VP1 epitopes of RV-A and RV-C.
Regardless of children's clinical status, all children that responded to the in vitro stimulation (>90%) had a similar magnitude of CD4+ T-cell responses to RV-A and RV-C. However, asthmatic children had a significantly lower number of circulating regulatory T cells (Tregs), and healthy controls had significantly more Tregs induced by RV-A than RV-C.
The comparable recall memory T-cell responses in asthmatic and control children to both RV-A and RV-C show that differences in the antibody and inflammatory responses previously described are likely to be due to regulation, with a demonstrated candidate being reduced regulatory T-cells. The reduced Treg numbers demonstrated here could explain the asthmatic's inability to appropriately control immunopathological responses to RV infections.
鼻病毒(RV)A 型和 C 型感染是哮喘恶化的最常见原因,也是其他急性和慢性呼吸道疾病恶化的主要原因。这两种病毒在学龄前和学龄儿童中都很常见,尤其是对于 RV-C,它可能导致严重的症状和住院治疗的需要。虽然 RV 感染与哮喘之间的关联已得到充分证实,但 RV 感染影响哮喘恶化的适应性免疫机制仍有待确定。
本研究旨在描述和比较 RV-A 和 RV-C 的 T 细胞反应,并检验 T 细胞反应在哮喘儿童和健康对照者之间存在差异的假设。
使用多参数流式细胞术检测急性哮喘儿童(n=22)和健康对照者(n=26)PBMC 中针对 RV-A 和 RV-C 的体外回忆性 T 细胞反应。反应由含有 RV-A 和 RV-C 特异性 VP1 表位的肽池诱导。
无论儿童的临床状况如何,所有对体外刺激有反应(>90%)的儿童对 RV-A 和 RV-C 的 CD4+T 细胞反应具有相似的幅度。然而,哮喘儿童的循环调节性 T 细胞(Tregs)数量显著降低,而健康对照者的 RV-A 诱导的 Tregs 数量明显多于 RV-C。
哮喘和健康对照儿童对 RV-A 和 RV-C 均具有相似的回忆性记忆 T 细胞反应,表明先前描述的抗体和炎症反应的差异可能是由于调节所致,其中一个候选调节机制是 Treg 细胞数量减少。这里显示的 Treg 数量减少可以解释哮喘患者无法适当控制对 RV 感染的免疫病理反应的原因。